The experiments proposed in this application are designed to gain insight into the process of differentiation during embryonic development. An understanding of morphogenesis, of cytodifferentiation, and of the relationship between these processes, is essential for ultimate understanding of the regulation of embryonic development. The relationship between morphogenesis and cytodifferentiation will be explored by continuing to determine the degree to which the regulation of pancreatic cytodifferentiation is independent of morphogenesis, and by determining if alteration of lung morphogenesis results in concomitant alteration of lung cytodifferentiation. The presence and roles of actin and myosin in morphogenetically active organ epithelia will be investigated for analysis of their relationship to microfilaments and morphogenetic contractile activities. The possible role of calcium ions in regulating these contractile systems will also be determined. The role of cyclic AMP in regulating microtubule and microfilament involvement in single cell locomotion will be tested, and the different functions of the microfilament network and sheath will be analyzed. The involvement and functions of extracellular macromolecules in cell movement and epithelial morphogenesis will be investigated. The requirement for, and consequence of, mucopolysaccharides in single cell locomotion will be analyzed, and the relative involvement of collagen and mucopolysaccharides in organogenesis will be determined. Finally, the role of mitosis and critical tissue mass in differentiation will be ascertained. Particularly, the possibility that mitotic activity is essential for pancreatic morphogenesis will be investigated.